As of this report, the NIAAA Repository/Screening Database includes phenotype and/or genomic data on more than 2500 individuals. Phenotype data include psychiatric diagnoses, a number of alcohol-related assessments and measures including lifetime and recent consumption and alcohol response phenotypes, personality and impulsivity measures, depression and anxiety symptoms, current and early life stress and trauma, aggression, suicidality, smoking, IQ, sleep quality, pain, and overall quality of life. Laboratory/biochemical measures are also available. Genomic data include 1) large-scale single nucleotide polymorphism (SNP) genotyping performed using Illumina arrays, and 2) exome sequencing of a subset of subjects, both via a partnership between the Clinical Core Laboratory of the OCD, and the Laboratory of Neurogenetics (NIAAA). All NIAAA PIs are encouraged to submit data requests in order to conduct research projects and analyses using the shared NIAAA Repository/Screening Database. Projects are logged and the status is tracked from initial request to manuscript publication. In addition, Human and Genomic data are shared via BTRIS and other mechanisms, including collaboration with NIH-supported consortia (PGC Alcoholism, ENIGMA) to ensure data sharing. Development of standardized assessments of alcohol responses (Mini alcohol screening exam -MASE), neurobiological changes during the addiction cycle (Addictions Neuroclinical Assessment -ANA) and measures of addiction are proceeding via the natural history protocol and also via neuroimaging studies in the OCD Neuroimaging core (PI, Reza Momenan). Data collection for the ANA was initiated in July 2018. Using the clinical database, factor and pathway analyses are being performed to identify factors, and clinical subgroups within patients with AUD who are heterogeneous both etiologically and in terms of clinical outcome. I. Projects (5) resulting in manuscripts published within the past year: The major depressive disorder GWAS-supported variant rs10514299 in TMEM161B-MEF2C predicts putamen activation during reward processing in alcohol dependence Impulsivity mediates the relationship of adult attention deficit hyperactivity symptoms and alcohol dependence severity Genetic association and expression analyses of the Phosphatidylinositol-4-Phosphate 5-Kinase (PIP5K1C) gene in alcohol use disorder relevance for pain signaling and alcohol use Association analysis of genetic variation in GATA Binding Protein 4 (GATA4) and alcohol use disorder Association of serum zinc with markers of liver injury in very heavy drinking alcohol-dependent patients II. Projects (7) resulting in manuscript submissions, or publications in press, within the past year: Stress vulnerability and alcohol use and consequences: from human laboratory studies to clinical outcomes (in press) Assessment of Addictions Neuroclinical Assessment (ANA) domains using measures from the current NIAAA screening protocol Genetic variation in FKBP5 influences cortisol levels in individuals with alcohol use disorder Decision making differences and alcohol use severity: the relationship between delay discounting and risky drinking Elevated stearoyl-CoA desaturase 1 activity is associated with alcoholic liver disease A role for the CD38 rs3796863 polymorphism in alcohol and monetary reward: possible involvement of dopamine signaling Alcohol dependence and severity are associated with self-reported aggression III. Projects (6) with manuscripts in preparation: Early life stress is associated with suicidality in alcoholic inpatients Effects of the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile on severity of alcohol dependence and stress response in alcohol-dependent subjects. Genetics and epigenetics of the dopamine transporter (DAT) in alcohol use disorder Obsessive craving as a predictor of suicidal ideation in alcohol dependent inpatients Calcium as a modulator of alcohol use disorder and the response to Acamprosate Evaluation of relationship between craving and DSM-IV criteria for AUD, sleep, pain, social support and co morbid AXIS-1 diagnoses IV. Ongoing projects (11) still in progress: GABA (GABBR1 and GABBR2) and GABA transporter 1 (GAT1) genetic variation in alcoholism and alcohol-related phenotypes. Data analyses are ongoing. Association between DCC netrin 1 receptor (DCC) and synuclein alpha (SNCA) genes and measures of impulsive behavior in alcoholic patients and controls. Data analyses are ongoing. Comparison of resting state functional connectivity, alcohol consumption patterns, and CASE behavior as a function of CHRNA5 genotype. Data analyses are ongoing Exome sequencing of alcoholic inpatients with low and high withdrawal. Sequencing is nearly complete. Genetics of vasopressin and vasopressin receptors in alcoholism. Data analyses are ongoing. The role of C-Reactive protein in alcohol use disorder. Data analyses are ongoing. Free peptide and receptor genotype of the appetitive hormones, leptin and amylin, and their association with alcohol-related phenotypes. Data analyses are ongoing. GWAS and pathway-informed analysis of externalizing behaviors. Data analyses are ongoing. Sex differences in glucose and insulin signaling and their association with trait aggression in individuals with and without alcohol use disorder. Data analyses are ongoing. Genetics of Alcohol Use Disorder with comorbid mood and anxiety disorders. Data analyses are ongoing. Comparison of personality measures between individuals with alcohol dependence, regular alcohol use and no alcohol use. Data analyses are ongoing. V. New projects (14) initiated within the past year: Electrocardiogram and other cardiovascular indicators of at-risk alcohol drinking Role of current stress and perceived stress in alcohol-dependence severity and quality of life: an update to the study of childhood trauma in alcohol use disorder Binge drinking behavior as a function of risk factors for alcohol use disorder Understanding compulsive drinking in humans Differences in withdrawal severity and craving in relation to successive detoxifications amongst treatment-seeking alcohol dependent Individuals Association between LRRK2 gene and compulsive behavior in alcoholic patients An imaging genetics study of the prepro-ghrelin and glucagon-like peptide-1 receptor gene variants in alcohol use disorder Neurobiological substrates of racial/ethnic disparity in alcohol use disorder: characterization of vulnerability/resilience via imaging, genetics, and biobehavioral information The relationship between CNR1 polymorphisms and alcohol abuse Effects of TSPO genotype on perceived stress, anxiety, and alcohol drinking behavior Characterization of drinking patterns in alcohol use disorder by Timeline Follow-Back variability analysis: the association with craving, nicotine/cannabinoids/other substance use, psychopathology, treatment seeking, cirrhosis and other alcohol-related liver conditions Association between dopaminergic genetic variation and IV alcohol consumption in the lab and in the field PNPLA3, drinking behavior, and metabolic parameters in alcoholics Reporting of adverse childhood events as a function of race/ethnicity and gender and their influence on drinking behaviors. VI. Other Progress As a result of the collaboration established last year with the Psychiatric Genetics Consortium (PGC), a manuscript is now in press that includes data from the NIAAA Repository/Screening Database. A new collaboration was also established with Indiana University and the Centenary Institute in Australia. Data from the NIAAA Repository/Screening Database, including large-scale genomic data and phenotype data, were shared with these collaborators.